The upper airway consists of three general regions: the nose, the pharynx, and the glottis. Each of these areas comprise a major site of airflow resistance. Muscles at these points can modulate upper airway caliber and compliance and, consequently, flow resistance during breathing. The precise neural organization of the control of upper airway muscles is unknown, but there is evidence to suggest that upper airway muscle activity is modulated by respiratory chemical drive as well as non-chemical reflexes. The purpose of the proposed research is to investigate and characterize the regulation of the activity of upper airway muscles and the factors that control the coordination of upper airway and chest wall muscles to maintain airway caliber and patency and ensure the adequacy of ventilation. In anesthetized animals we intend to perform interventions designed to characterize basic mechanisms in the respiratory activation and coordiantion of upper airway muscles. Electromyographic activity from these muscles innervated by various cranial nerves will be compared to activity from the diaphragm under resting conditions and in response to increased chemical drive by hypoxia or hypercapnia. In addition, muscle activity will be compared in response to changing lung volume, to vagotomy, to chest wall reflex activation, and to upper airway mechano-receptor activation. Similar studies, appropriately modified, will be carried out in normal human subjects and in patients in whom the upper airways are by-passed. Studies will be carried out in subjects during sleep to compare responses during wakefulness with those during different stages of sleep. Studies of the control of upper airway muscle activation particularly during wakefulness and also during sleep will be performed in patients with obstructive apneas to identify any differences between these patients and healthy subjects. This research will provide important basic information regarding control mechanisms regulating the activity of upper airway muscles and the effects of sleep on this respiratory control system. The results of these studies may further the understanding of the neuromuscular factors responsible for the maintenance of airway patency.